PAR-4/Ca
Biomarkers
/ blood
Blood Glucose
/ metabolism
Blood Platelets
/ drug effects
Calcium
/ metabolism
Calpain
/ metabolism
Case-Control Studies
Cell-Derived Microparticles
/ drug effects
Diabetes Mellitus, Type 2
/ blood
Female
Glycated Hemoglobin
/ metabolism
Humans
Interleukin-6
/ metabolism
Macrophages
/ metabolism
Male
Middle Aged
Platelet Activation
/ drug effects
Receptors, Thrombin
/ agonists
THP-1 Cells
Thrombin
/ pharmacology
Extracellular vesicles
Glycated hemoglobin
NF-kB
Platelet activation
THP-1 transformed macrophages
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
03 04 2021
03 04 2021
Historique:
received:
18
12
2020
accepted:
22
03
2021
entrez:
4
4
2021
pubmed:
5
4
2021
medline:
7
10
2021
Statut:
epublish
Résumé
Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages. In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages. We found that MPs CD62P These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.
Sections du résumé
BACKGROUND
Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages.
METHODS
In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages.
RESULTS
We found that MPs CD62P
CONCLUSIONS
These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.
Identifiants
pubmed: 33812377
doi: 10.1186/s12933-021-01267-w
pii: 10.1186/s12933-021-01267-w
pmc: PMC8019350
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Glycated Hemoglobin A
0
IL6 protein, human
0
Interleukin-6
0
Receptors, Thrombin
0
hemoglobin A1c protein, human
0
Thrombin
EC 3.4.21.5
Calpain
EC 3.4.22.-
protease-activated receptor 4
JWE1M73YZN
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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